Relationship between microcystin production and cell division rates in nitrogen-limited Microcystis aeruginosa cultures

Analysis of changes over time in microcystin content of nitrogen-limited Microcystis aeruginosa (Kutzing) Lemmermann batch cultures (strain MASH01-A19) showed that net microcystin production was limited to the phase of growth when cell concentration was increasing. The net microcystin production rate decreased as the specific cell division rate (mu(c)) decreased, but, more importantly, the specific toxin production rate (mu(MCYST)) decreased at an identical rate to that of mu(c) when the culture became nitrate-limited. The actual size of the microcystin pool (total culture microcystin concentration) increased while cells were dividing, then remained constant or decreased only slightly during the stationary and death phases, even when the cultures were severely nitrate-starved. These findings demonstrate conclusively that the processes of cell division and microcystin production are tightly coupled under nitrogen-limited cell division. Our findings suggest that microcystin production is controlled by environmental effects on the rate of cell division, not through any direct effect on the metabolic pathways of toxin production. Reevaluation of data presented by others shows this to be the case for two other cyanobacterial species producing nine different microcystins over a wide range of environmental variables. We believe these relationships now provide a unifying view of environmental control of microcystin production in hepatotoxic cyanobacteria. We conclude that there is a direct linear correlation between cell division and microcystin production rates in all microcystin-producing cyanobacteria regardless of the environmental factor that is limiting cell division. We also conclude that microcystin is not a secondary metabolite, as is currently thought, but that it displays many of the attributes of essential intracellular nitrogenous compounds in toxigenic cyanobacteria.